So Many Roads: the Multifaceted Regulation of Autophagy Induction.

摘要: Autophagy is an evolutionary conserved, degradative process from single-cell eukaryotes, such as Saccharomyces cerevisiae, to higher mammals, humans. The regulation of autophagy has been elucidated through the combined study yeast, Caenorhabditis elegans, mice, Drosophila melanogaster, and MTOR, major negative regulator autophagy, activating nutrient kinases, 5'-AMP-activated protein kinase (AMPK), interact with regulatory complex: ULK1/2, RB1CC1, ATG13, ATG101. ULK1/2 complex induces by phosphorylating downstream complexes, BECN1 PIK3 signaling that leads creation LC3+ autophagosomes. We highlight in this review various reports induction are independent these regulators. discuss MTOR-independent, AMPK-independent, ULK1/2-independent, BECN1-PIK3C3-independent autophagy. illustrate components required vary nature signal type cell do not always require canonical members pathway. rather than thinking a linear pathway, it better think interconnecting web key regulators, many which can induce different requirements depending on length signals.